Editing Cisapride

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 460039920
| IUPAC_name = (±)-''cis''-4-amino-5-chloro-''N''-(1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl)-2-methoxybenzamide
| image = Cisapride enantiomers labelled.svg
| image_class = skin-invert-image
| width = 350px
| image2 = Cisapride enantiomers ball-and-stick models from xtal 1997.png
| width2 = 350px
<!--Clinical data-->
| tradename =  Prepulsid, Propulsid
| Drugs.com = {{drugs.com|pro|propulsid}}
| MedlinePlus = a694006
| pregnancy_AU = B1
| pregnancy_category = 
| legal_AU = S4
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_UK = POM
| legal_US_comment = Withdrawn
| legal_status = 
| routes_of_administration = [[Oral administration|By mouth]] (tablets), suspension
<!--Pharmacokinetic data-->
| bioavailability = 30-40%
| protein_bound = 97.5%
| metabolism = liver [[CYP3A4]], intestinal
| elimination_half-life = 10 hours
| excretion = kidney, bile duct
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 81098-60-4
| ATC_prefix = A03
| ATC_suffix = FA02
| ATC_supplemental =  
| PubChem = 2769
| IUPHAR_ligand = 240
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00604
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2667
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = UVL329170W
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00274
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1729
<!--Chemical data-->
| C=23 | H=29 | Cl=1 | F=1 | N=3 | O=4
| smiles = Clc1cc(c(OC)cc1N)C(=O)NC3CCN(CCCOc2ccc(F)cc2)CC3OC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C23H29ClFN3O4/c1-30-21-13-19(26)18(24)12-17(21)23(29)27-20-8-10-28(14-22(20)31-2)9-3-11-32-16-6-4-15(25)5-7-16/h4-7,12-13,20,22H,3,8-11,14,26H2,1-2H3,(H,27,29)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DCSUBABJRXZOMT-UHFFFAOYSA-N
}}
'''Cisapride''' is a [[gastroprokinetic agent]], a [[pharmaceutical drug|drug]] that increases [[motility]] in the upper [[gastrointestinal tract]]. It acts directly as a [[serotonin]] [[5-HT4 receptor|5-HT<sub>4</sub> receptor]] [[agonist]] and indirectly as a [[parasympathomimetic]]. Stimulation of the serotonin receptors increases [[acetylcholine]] release in the [[enteric nervous system]]. It has been sold under the trade names '''Prepulsid''' (Janssen-Ortho) and '''Propulsid''' (in the United States). It was discovered by [[Janssen Pharmaceuticals]] in 1980.  In many countries, it has been either withdrawn from the market or had its indications limited due to incidence of serious cardiac side-effects.<ref>{{Cite web|title=Propulsid To Go Off Market - Warning|url=https://www.medicinenet.com/propulsid_to_go_off_market_-_warning/views.htm|access-date=2021-12-25|website=MedicineNet|language=en}}</ref>  Propulsid was linked to children's deaths.<ref>{{Cite web|date=2000-12-20|title=PROPULSID: A Heartburn Drug, Now Linked to Children's Deaths|url=https://www.latimes.com/nation/la-122001propulsid-story.html|access-date=2021-12-25|website=Los Angeles Times|language=en-US}}</ref>

The commercial preparations of this drug are the [[racemic]] mixture of both [[enantiomer]]s of the compound. The (+) enantiomer itself<!-- what is the absolute configuration? --> has the major pharmacologic effects and does not induce many of the detrimental side-effects of the mixture.<ref>{{US patent reference |number = 5955478 |y=  1999 |m= Sep |d= 21 | inventor = Gray NM, Young JW |title= Methods for treating gastrointestinal motility dysfunction using optically pre (+) cisapride }}</ref>

==Medical uses==
Cisapride has been used for the treatment of [[gastroesophageal reflux disease]] (GERD). There is no evidence it is effective for this use in children.<ref name=GERD2010>{{cite journal | vauthors = Maclennan S, Augood C, Cash-Gibson L, Logan S, Gilbert RE | title = Cisapride treatment for gastro-oesophageal reflux in children | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD002300 | date = April 2010 | volume = 2010 | pmid = 20393933 | doi = 10.1002/14651858.CD002300.pub2 | pmc = 7138252 | url = https://researchonline.lshtm.ac.uk/3792/1/3792.pdf }}</ref> It also increases gastric emptying in people with diabetic [[gastroparesis]]. Evidence for its use in [[constipation]] is not clear.<ref name=Cochrane2011>{{cite journal | vauthors = Aboumarzouk OM, Agarwal T, Antakia R, Shariff U, Nelson RL | title = Cisapride for intestinal constipation | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD007780 | date = January 2011 | pmid = 21249695 | doi = 10.1002/14651858.CD007780.pub2 }}</ref>

In many countries, it has been either withdrawn or had its indications limited because of reports of the side-effect [[long QT syndrome]], which may cause [[Heart arrhythmia|arrhythmia]]s. The [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) issued a warning letter to doctors,<ref>{{cite web
|url = https://www.medscape.com/viewarticle/783710
|title = "Cardiac contraindications included in new FDA warnings about Propulsid"
|author = 
|date = January 25, 2000
|publisher = medscape.com
|accessdate = 10 May 2021
}}</ref> and cisapride was voluntarily removed from the U.S. market on July 14, 2000. Its use in Europe has also been limited.<ref name=GERD2010/> It was banned in India and in the Philippines in 2011.<ref name=ban>{{cite web|url=http://cdsco.nic.in/html/drugsbanned.html|title=Drugs banned in India|publisher=Central Drugs Standard Control Organization, Dte.GHS, Ministry of Health and Family Welfare, Government of India|access-date=2013-09-17|url-status=dead|archive-url=https://web.archive.org/web/20150221053621/http://cdsco.nic.in/html/drugsbanned.html|archive-date=2015-02-21}}</ref>

==Veterinary uses==
Cisapride is still available in the United States and Canada for use in animals, and is commonly prescribed by veterinarians to treat [[megacolon]] in cats.

Cisapride is also commonly used to treat GI stasis in rabbits, sometimes in conjunction with [[metoclopramide]] (Reglan).

==Kinetics==
Oral [[bioavailability]] of cisapride is approximately 33%. It is inactivated primarily by hepatic metabolism by [[CYP3A4]] with a half-life of 10 hours. The dose of the drug should be reduced in case of liver diseases.<ref name="pmid2373139">{{cite journal | vauthors = Hedner T, Hedner J, Gelin-Friberg A, Huang ML, Van de Poel S, Woestenborghs R, Van Peer A, Heykants J | title = Comparative bioavailability of a cisapride suppository and tablet formulation in healthy volunteers | journal = European Journal of Clinical Pharmacology | volume = 38 | issue = 6 | pages = 629–31 | date = 1990 | pmid = 2373139 | doi = 10.1007/bf00278595 | s2cid = 33641651 }}</ref>

==Pharmacology and mechanism of action==

As a [[prokinetic agent]] that increases [[gastrointestinal motility]], cisapride acts as a selective [[serotonin agonist]] in the 5-HT<sub>4</sub> receptor subtype. Cisapride also relieves constipation-like symptoms by indirectly stimulating the release of [[acetylcholine]], which acts on [[muscarinic receptor]]s.

== See also ==
*[[Domperidone]]
*[[Drug of last resort]]
*[[Laxative#Serotonin agonist|Serotonin-agonising laxatives]]
*[[Benzamide]]
*[[Itopride]]
*[[Metoclopramide]]
*[[Mosapride]]
*[[Prucalopride]]

== References ==
{{reflist}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Brenner GM | date = 2000 | title = Pharmacology | location = Philadelphia, PA | publisher = W.B. Saunders Company | isbn = 0-7216-7757-6 }}
* {{cite book | author = Canadian Pharmacists Association | date = 2000 | title = Compendium of Pharmaceuticals and Specialties | edition = 25th | location = Toronto, ON | publisher = Webcom | isbn = 0-919115-76-4 }}
* {{cite web | title = Cisapride | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a694006.html | work = Medline Plus | publisher = U.S. National Library of Medicine }}
{{refend}}

== External links ==
* [http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=13266 Archived Drug Label]

{{Propulsives}}
{{Serotonergics}}
{{Cholinergics}}
{{Ion channel modulators}}

[[Category:4-Amino-N-(3-(diethylamino)propyl)-2-methoxybenzamides]]
[[Category:Serotonin receptor agonists]]
[[Category:HERG blocker]]
[[Category:CYP2D6 inhibitors]]
[[Category:Withdrawn drugs]]
[[Category:Chloroarenes]]
[[Category:Piperidines]]
[[Category:4-Fluorophenyl compounds]]
[[Category:Janssen Pharmaceutica]]
[[Category:Belgian inventions]]